Compositions containing chalcones and use thereof

ABSTRACT

The present invention features composition comprising a chalcone and the use thereof for treating acne and reducing the appearance of oil or pores on the skin, hair and scalp.

BACKGROUND OF THE INVENTION

Acne disorders are often classified as noninflammatory or inflammatorytypes. Noninflammatory acne is characterized by closed comedones(whiteheads) and open comedones (blackheads), consisting of compactmasses of keratin, sebum, and bacteria, which dilate the follicularduct. A comedone forms when a pilo-sebaceous duct is obstructed and/orwhen there is increased production of sebum by a sebaceous gland.Formation of the comedone can be followed by inflammation, resultingfrom bacterial proliferation and/or overproduction of sebum. Typically,the bacteria are anaerobic bacteria such as Propionibacteria (P. acnes).Inflammatory acne is characterized by papules (pimples), pustules, andnodulocystic lesions, which may lead to scarring. Several factors arebelieved to play important roles in the pathogenesis of acne including:sebum production, hormonal stimulation, plugged pores, and skinpathogens. Sebum levels are increased in subjects with acne byapproximately 70% compared to sebum levels of control subjects.

The present invention relates to the unexpected discovery that certainchalcones are topically effective for treating acne and reducing theappearance of oil or pores on the skin.

SUMMARY OF THE INVENTION

In one aspect, the present invention features a method of treating acneor reducing the appearance of oil or pores on the skin by administeringto skin in need of such treatment a composition including a chalcone ofFormula I

wherein,

R is hydrogen, C₁-C₆ alkyl, C₂-C₁₀ alkenyl, acyl or glycosyl, and

m is 0 to 5; and

n is 0 to 5;

or a cosmetically-acceptable salt thereof; provided that the sum of mand n is greater than or equal to 4.

In one aspect, the present invention features a method of treating acneor reducing the appearance of oil or pores on the skin by administeringto skin in need of such treatment a composition comprising

(a) a chalcones of Formula I

wherein,

R is hydrogen, C₁-C₆ alkyl, C₂-C₁₀ alkenyl, acyl or glycosyl, and

m is 0 to 5;

n is 0 to 5;

or a cosmetically-acceptable salt thereof; and(b) a catechin.

In another aspect, the present invention features a product including(a) such a composition and (b) instructions directing the user toadminister said composition to skin in order to treat acne or reduce theappearance of oil or pores on the skin.

In another aspect, the present invention features a method of promotingsuch a composition by directing the user to administer said compositionto skin in order to treat acne or reduce the appearance of oil or poreson the skin.

Other features and advantages of the present invention will be apparentfrom the detailed description of the invention and from the claims.

DETAILED DESCRIPTION OF THE INVENTION

It is believed that one skilled in the art can, based upon thedescription herein, utilize the present invention to its fullest extent.The following specific embodiments are to be construed as merelyillustrative, and not limitative of the remainder of the disclosure inany way whatsoever.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the invention belongs. Also, all publications, patentapplications, patents, and other references mentioned herein areincorporated by reference. Unless otherwise indicated, a percentagerefers to a percentage by weight (i.e., % (W/W)).

Definitions

What is meant by “treating acne” is reducing or preventing acne orrosacea.

What is meant by a “product” is a product in finished packaged form. Inone embodiment, the package is a container such as a plastic, metal orglass tube or jar containing the composition. The product may furthercontain additional packaging such as a plastic or cardboard box forstoring such container. In one embodiment, the product containsinstructions directing the user to apply the composition to (i) treatacne or (ii) reduce the appearance of oil or pores on the skin.

What is meant by “promoting” is promoting, advertising, or marketing.Examples of promoting include, but are not limited to, written, visual,or verbal statements made on the product or in stores, magazines,newspaper, radio, television, internet, and the like.

For promoting the treatment of acne, examples of such statementsinclude, but are not limited to, “treats acne,” “prevents acne,”“reduces acne lesions, comedones, or pimples,” “reduces the appearanceof acne lesions, comedones, or pimples,” “reduces the appearance of acnebreakouts and blemishes,” “preventing, controlling or regulating theappearance of acne breakouts and blemishes”, and “reduces breakouts andblemishes.”

For promoting the reduction in the appearance of oil on the skin,examples of such statements include, but are not limited to, “reducesthe appearance of sebum,” “preventing, controlling or regulating theproduction of sebum,” “reduces sebum,” “reduces the appearance ofoily/shiny skin,” “reduces the appearance of greasy skin,” and “reducesshine on the skin, hair, or scalp.” In one embodiment, the compositionis applied to skin not in need of treatment for acne (i.e., skin notsuffering from acne or the scalp/hair).

For promoting the reduction in the appearance of pores on the skin,examples of such statements include, but are not limited to, “reducesthe size of pores,”“minimizes the appearance of pores,” “refines theappearance of pores,” “reduces the visibility or pores,” and “closespore opening.” In one embodiment, the composition is applied to skin notin need of treatment for acne (i.e., skin not suffering from acne).

As used herein, “administering to skin in need of such treatment” meanscontacting (e.g., by use of the hands or an applicator such, but notlimited to, a wipe, tube, roller, spray, or patch) the area of skin inneed such treatment or an area of skin proximate to the area of skin inneed of such treatment.

As used herein, “composition” means a composition suitable foradministration to the skin.

As used herein, “cosmetically-acceptable” means that the ingredientswhich the term describes are suitable for use in contact with the skinwithout undue toxicity, incompatibility, instability, irritation,allergic response, and the like.

As used herein, “safe and effective amount” means an amount of thecompound, carrier, or of the composition sufficient to induce anenhancement in tissue elasticity, but low enough to avoid serious sideeffects. The safe and effective amount of the compounds or compositionwill vary with the area being treated, the age, health and skin type ofthe end user, the duration and nature of the treatment, the specificcompound or composition employed, the particular cosmetically-acceptablecarrier utilized, and like factors.

Compounds

The compositions of the present invention contain at least one compoundof the formula I a chalcone of Formula I

wherein,

R is hydrogen, C₁-C₆ alkyl, C₂-C₁₀ alkenyl, acyl or glycosyl, and

m is 0 to 5; and

n is 0 to 5;

or a cosmetically-acceptable salt thereof.

In one embodiment, the sum of m and n is greater than or equal to 4(such as equal to 4, 5 or 6)

Examples of compounds of formula I include, but are not limited to,those compounds set forth below in Table 1 of Example 1.

The compounds of the present invention may also be present in the formof cosmetically acceptable salts. For use in medicine, the salts of thecompounds of this invention refer to non-toxic “cosmetically acceptablesalts,” cosmetically acceptable acidic/anionic or basic/cationic salts.Cosmetically acceptable acidic/anionic salts include, and are notlimited to acetate, benzenesulfonate, benzoate, bicarbonate, bitartrate,bromide, calcium edetate, camsylate, carbonate, chloride, citrate,dihydrochloride, edetate, edisylate, estolate, esylate, fumarate,glyceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate,hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide,isethionate, lactate, lactobionate, malate, maleate, mandelate,mesylate, methylbromide, methylnitrate, methylsulfate, mucate,napsylate, nitrate, pamoate, pantothenate, phosphate/diphospate,polygalacturonate, salicylate, stearate, subacetate, succinate, sulfate,tannate, tartrate, teoclate, tosylate and triethiodide. Cosmeticallyacceptable basic/cationic salts include, and are not limited toaluminum, benzathine, calcium, chloroprocaine, choline, diethanolamine,ethylenediamine, lithium, magnesium, meglumine, potassium, procaine,sodium and zinc. Other salts may, however, be useful in the preparationof compounds according to this invention or of their cosmeticallyacceptable salts. Organic or inorganic acids also include, and are notlimited to, hydriodic, perchloric, sulfuric, phosphoric, propionic,glycolic, methanesulfonic, hydroxyethanesulfonic, oxalic,2-naphthalenesulfonic, p-toluenesulfonic, cyclohexanesulfamic,saccharinic or trifluoroacetic acid.

In one embodiment, the compositions of present invention contain fromabout 0.01% to about 10% by weight of such compound, such as from about0.1% to about 5% by weight of such compound, such as from about 0.5% toabout 3% by weight of such compound. In one embodiment, the compositioncontains at least 1% by weight of such compound, such as at least about2% by weight of such compound. The compounds of the invention may besynthesized by those having ordinary skill in the art and/or purchasedfrom commercial sources such as Indofine Chemicals Inc. (Somerville,N.J.).

Compositions

The compositions useful in the present invention involve formulationssuitable for administering to the target tissues, such as mammalian skinsuch as human skin. In one embodiment, the composition contains a safeand effective amount of (i) a chalcone of formula I and (ii) acosmetically-acceptable carrier. In one embodiment, thecosmetically-acceptable carrier is from about 50% to about 99.99%, byweight, of the composition (e.g., from about 80% to about 99%, byweight, of the composition).

The compositions may be made into a wide variety of product types thatinclude but are not limited to solutions, suspensions, lotions, creams,gels, toners, sticks, sprays, ointments, cleansing liquid washes andsolid bars, shampoos and hair conditioners, pastes, foams, powders,mousses, shaving creams, wipes, strips, patches, electrically-poweredpatches, wound dressing and adhesive bandages, hydrogels, film-formingproducts, facial and skin masks, make-up such as foundations, eyeliners, and eye shadows, and the like. These product types may containseveral types of cosmetically-acceptable carriers including, but notlimited to solutions, suspensions, emulsions such as microemulsions andnanoemulsions, gels, solids and liposomes. The following arenon-limitative examples of such carriers. Other carriers can beformulated by those of ordinary skill in the art.

The compositions useful in the present invention can be formulated assolutions. Solutions typically include an aqueous or organic solvent(e.g., from about 50% to about 99.99% or from about 90% to about 99% ofa cosmetically acceptable aqueous or organic solvent). Examples ofsuitable organic solvents include: propylene glycol, polyethylene glycol(200-600), polypropylene glycol (425-2025), glycerol, 1,2,4-butanetriol,sorbitol esters, 1,2,6-hexanetriol, ethanol, and mixtures thereof.

A lotion can be made from such a solution. Lotions typically containfrom about 1% to about 20% (e.g., from about 5% to about 10%) of anemollient(s) and from about 50% to about 90% (e.g., from about 60% toabout 80%) of water. As used herein, “emollients” refer to materialsused for the prevention or relief of dryness, as well as for theprotection of the skin or hair. Examples of emollients include, but arenot limited to, those set forth in the International Cosmetic IngredientDictionary and Handbook, eds. Wenninger and McEwen, pp. 1656-61, 1626,and 1654-55 (The Cosmetic, Toiletry, and Fragrance Assoc., Washington,D.C., 7^(th) Edition, 1997) (hereinafter “ICI Handbook”).

Another type of product that may be formulated from a solution is acream. A cream typically contains from about 5% to about 50% (e.g., fromabout 10% to about 20%) of an emollient(s) and from about 45% to about85% (e.g., from about 50% to about 75%) of water.

Yet another type of product that may be formulated from a solution is anointment. An ointment may contain a simple base of animal, vegetable, orsynthetic oils or semi-solid hydrocarbons. An ointment may contain fromabout 2% to about 10% of an emollient(s) plus from about 0.1% to about2% of a thickening agent(s). Examples of thickening agents include, butare not limited to, those set forth in the ICI Handbook pp. 1693-1697.

The compositions useful in the present invention can also be formulatedas emulsions. If the carrier is an emulsion, from about 1% to about 10%(e.g., from about 2% to about 5%) of the carrier contains anemulsifier(s). Emulsifiers may be nonionic, anionic or cationic.Examples of emulsifiers include, but are not limited to, those set forthin the ICI Handbook, pp. 1673-1686.

Lotions and creams can be formulated as emulsions. Typically suchlotions contain from 0.5% to about 5% of an emulsifier(s), while suchcreams would typically contain from about 1% to about 20% (e.g., fromabout 5% to about 10%) of an emollient(s); from about 20% to about 80%(e.g., from 30% to about 70%) of water; and from about 1% to about 10%(e.g., from about 2% to about 5%) of an emulsifier(s).

Single emulsion skin care preparations, such as lotions and creams, ofthe oil-in-water type and water-in-oil type are well-known in the artand are useful in the subject invention. Multiphase emulsioncompositions, such as the water-in-oil-in-water type or theoil-in-water-in-oil type, are also useful in the subject invention. Ingeneral, such single or multiphase emulsions contain water, emollients,and emulsifiers as essential ingredients.

The compositions of this invention can also be formulated as a gel(e.g., an aqueous, alcohol, alcohol/water, or oil gel using a suitablegelling agent(s)). Suitable gelling agents for aqueous and/or alcoholicgels include, but are not limited to, natural gums, acrylic acid andacrylate polymers and copolymers, and cellulose derivatives (e.g.,hydroxymethyl cellulose and hydroxypropyl cellulose). Suitable gellingagents for oils (such as mineral oil) include, but are not limited to,hydrogenated butylene/ethylene/styrene copolymer and hydrogenatedethylene/propylene/styrene copolymer. Such gels typically containsbetween about 0.1% and 5%, by weight, of such gelling agents.

The compositions of the present invention can also be formulated into asolid formulation (e.g., a wax-based stick, soap bar composition,powder, and wipe containing powder).

The compositions useful in the subject invention may contain, inaddition to the aforementioned components, a wide variety of additionaloil-soluble materials and/or water-soluble materials conventionally usedin compositions for use on skin at their art-established levels.

Additional Cosmetically Active Agents

In one embodiment, the composition further contains another cosmeticallyactive agent in addition to the above compounds. What is meant by a“cosmetically active agent” is a compound (e.g., a synthetic compound ora compound isolated from a natural source, or a natural extractcontaining a mixture of compounds) that has a cosmetic or therapeuticeffect on the tissue, including, but not limiting to, lightening agents,darkening agents such as self-tanning agents, anti-acne agents, shinecontrol agents, anti-microbial agents such as anti-yeast agents,anti-fungal, and anti-bacterial agents, anti-inflammatory agents,anti-parasite agents, external analgesics, sunscreens, photoprotectors,antioxidants, keratolytic agents, detergents/surfactants, moisturizers,nutrients, vitamins, energy enhancers, anti-perspiration agents,astringents, deodorants, hair removers, hair growth enhancing agents,hair growth delaying agents, firming agents, anti-callous agents, agentsfor skin conditioning, anti-cellulite agents, fluorides, andodor-control agents such as odor masking or pH-changing agents.

In one embodiment, the cosmetically active agent is selected from, butnot limited to, the group consisting of hydroxy acids, benzoyl peroxide,D-panthenol, octyl methoxycinnimate, titanium dioxide, octyl salicylate,homosalate, avobenzone, carotenoids, free radical scavengers, spintraps, retinoids and retinoid precursors such as retinol and retinylpalmitate, ceramides, polyunsaturated fatty acids, essential fattyacids, enzymes, enzyme inhibitors, minerals, hormones such as estrogens,steroids such as hydrocortisone, 2-dimethylaminoethanol, copper saltssuch as copper chloride, peptides containing copper such asCu:Gly-His-Lys, coenzyme Q10, amino acids such a proline, vitamins,lactobionic acid, acetyl-coenzyme A, niacin, riboflavin, thiamin,ribose, electron transporters such as NADH and FADH2, and otherbotanical extracts such as aloe vera, Feverfew, and Soy, and derivativesand mixtures thereof. The cosmetically active agent will typically bepresent in the composition of the invention in an amount of from about0.001% to about 20% by weight of the composition, e.g., about 0.005% toabout 10% such as about 0.01% to about 5%.

Examples of vitamins include, but are not limited to, vitamin A, vitaminBs such as vitamin B3, vitamin B5, and vitamin B12, vitamin C, vitaminK, vitamin E such as alpha, gamma or delta-tocopherol, and derivatives(such as salts and esters) and mixtures thereof.

Examples of hydroxy acids include, but are not limited, to glycolicacid, lactic acid, malic acid, salicylic acid, citric acid, and tartaricacid.

Examples of antioxidants include, but are not limited to, water-solubleantioxidants such as sulfhydryl compounds and their derivatives (e.g.,sodium metabisulfite and N-acetyl-cysteine), lipoic acid anddihydrolipoic acid, resveratrol, lactoferrin, and ascorbic acid andascorbic acid derivatives (e.g., ascorbyl palmitate and ascorbylpolypeptide). Oil-soluble antioxidants suitable for use in thecompositions of this invention include, but are not limited to,butylated hydroxytoluene, retinoids (e.g., retinol and retinylpalmitate), different types of tocopherols (e.g., alpha-, gamma-, anddelta-tocopherols and their esters such as acetate) and their mixtures,tocotrienols, and ubiquinone. Natural extracts containing antioxidantssuitable for use in the compositions of this invention, include, but notlimited to, extracts containing flavonoids, isoflavonoids, and theirderivatives such as genistein and diadzein (e.g., such as Soy and Cloverextracts, extracts containing resveratrol and the like. Examples of suchnatural extracts include grape seed, green tea, pine bark, and propolis.

Examples of enzymes include, but are not limited to, proteases such asfungal proteases, bacterial proteases or mammalian proteases. Examplesof such proteases include, but are not limited to, pepsin, cathepsin,human urinary acid protease, fungal proteases derived from Neurosporaoryzae, Mucor pusillus, Mucor miehei, Rhizopus chinensis, or Endothiaparasitica, and bacterial proteases rhizopuspepsin, penicillopepsin, andendothiapepsin. Further, the proteases may be derived from processesinvolving genetic engineering processes and techniques.

Examples of fungal extracts include, but are not limited to, extractsfrom Neurospora oryzae, Mucor pusillus, Mucor miehei, Rhizopuschinensis, or Endothia parasitica Mucor Miehei. Examples of compositionscontaining such proteases and fungal extracts are disclosed in U.S. Pat.No. 5,976,556.

Anti-Acne Agents

In one embodiment, the present invention relates to topical compositionsincluding an anti-acne agent. What is meant by an anti-acne agent is ancompound that has been approved by the U.S. Food and Drug Administrationfor the topical treatment of acne. Examples of anti-acne agents include,but are not limited to, salicylic acid, benzoyl peroxide, sulphur,retinoic acid, candida bombicola/glucose/methyl rapeseedate ferment,peat water, resorcinol, silt, peat, permethin, azelaic acid,clindamycin, adapalene, erythromycin, sodium sulfacetamide, andcombinations thereof. In one embodiment, the amount of anti-acne agentin the composition is from about 0.01% to about 10%, for example fromabout 0.1% to about 5%, or from about 0.5% to about 2% by weight, basedon the total weight of the composition.

Catechins

In one embodiment, the compositions of the present invention furthercontain a catechin. The term “catechin” refers to a polyphenolicsubstance that belongs to the flavan-3-ol class of flavonoids. Thecatechins may be synthetically made or naturally made (e.g., such aspart of a plant extract). Exemplary catechins include but are notlimited to, catechin (C), catechin gallate (CG), epicatechin (EC),gallocatechin (GC), gallocatechin gallate (GCG), epigallocatechin (EGC),epicatechin gallate (ECG), and epigallocatechin gallate (EGCG).Exemplary plants which have a content of catechins include but are notlimited to Catechu, Green Tea (Camellia sinensis, Camellia oleifera),Vitis vinifera, grape (Vitis vinifera), agrimony (Agrimonia eupatoria),cotton (Gossypium sp), black currant (Ribes nigrum), cowberry (Vacciniumvitis-idaea var. minus), Alpinia galanga and Alpinia katsumada.Catechins can be synthetically made or are available commercially, forexample from Indofine (Somerville, N.J.) or from Aldrich (Milwaukee,Wis.).

Plant Extract

In one embodiment, the compositions of present invention further containanother plant extract. What is meant by a “plant extract” is a blend ofcompounds isolated from a plant. Such compounds may be isolated from oneor more part of the plant (e.g., the whole plant, flower, seed, root,rhizome, stem, fruit and/or leaf of the plant) by physically removing apiece of such plant, such as grinding a flower of the plant. Suchcompounds may also be isolated from the plant by using extractionprocedures well known in the art (e.g., the use of organic solvents suchas lower C₁-C₈ alcohols, C₁-C₈ alkyl polyols, C₁-C₈ alkyl ketones, C₁-C₈alkyl ethers, acetic acid C₁-C₈ alkyl esters, and chloroform, and/orinorganic solvents such as water, inorganic acids such as hydrochloricacid, and inorganic bases such as sodium hydroxide).

In one embodiment, the plant extract (e.g., an alpinia extract, a greentea extract, a feverfew extract, an agrimony extract, a cotton extract,a grape extract, a black currant extract, a cowberry extract or asoybean extract) is present in the composition in an amount from about0.001% to about 20% by weight, in particular in an amount from about0.1% to about 10% by weight of the composition. Unless stated otherwise,the weight of the extract refers to the dry weight of the extract.

Feverfew Extract

In one embodiment, the compositions of present invention further containa feverfew extract. What is meant by a “feverfew extract” is a blend ofcompounds isolated from a feverfew plant. Examples of such compounds,include, but are not limited to, apigenin-7-glucoside,apigenin-7-glucuronide, 1-β-hydroxyarbusculin,6-hydroxykaempferol-3,7-4′-trimethylether (Tanetin),6-hydroxykaempferol-3,7-dimethyl ether, 8-β-reynosin, 10-epicanin,ascorbic acid, beta-carotene, calcium, chromium, chrysanthemolide,chrysanthemomin, chrysarten-A, chrsyarten-c, chrysoeriol-7-glucuronide,cobalt, cosmosiin, epoxyartemorin, luteolin-7-glucoside,luteolin-7-glucuronide, mangnoliolide, parthenolide,quercetagentin-3,7,3′-trimethylether, quercetagetin-3′7-dimethylether,reynosin, tanaparthin, tanaparthin-1α,4α-epoxide,tanaparthin-1β,4β-epoxide, β-costunolide, 3-β-hydroxy-parthenolide, and3,7,3′-trimethoxyquercetagetin. The α-unsaturated γ-lactones present inthe feverfew plant, such as parthenolide, are known to cause theallergic reactions. Therefore, in one embodiment, the feverfew extractis substantially free of the allergy causing α-unsaturated γ-lactones.The preparation of feverfew extract that is substantially free ofparthenolide is disclosed in Example 1 in U.S. Patent Application No.20040105905.

Soybean Extract

In one embodiment, the compositions of present invention further containa soybean extract. What is meant by a “soybean extract” is a blend ofcompounds isolated from soybean. The soybean extract may contain only aportion of the soybean (e.g., an extract of the soybean such as a lipidreduced soybean powder or filtered soymilk) or may contain the entiresoybean (e.g., a ground powder of the soybean). The soybean extract maybe in the form of a fluid (e.g., soymilk) or a solid (e.g., a soybeanpowder or soymilk powder).

The soybean extract may be soybean powder. Soybean powder may be made bygrinding dry soybeans. The soybean powder may be lyophilized. Soymilkand soymilk powder are also useful soybean extracts. Soymilk is acombination of solids derived from soybeans and water, the mixture ofwhich has some or all of the insoluble constituents filtered off.Soymilk powder is evaporated soymilk, which in one embodiment, is in alyophilized or spray-dried form. Procedures for manufacturing soymilkinclude, but are not limited to, the following three procedures. First,soymilk may be made by placing soybeans into water to allow them toabsorb the water. The swelled beans are then ground and additional wateris then added. The mixture may then be filtered to remove any insolubleresidue. Second, soymilk may also be prepared from soybean powder.Soybean powder is thoroughly mixed with water (e.g., for at least onehour), which may then be followed by a filtration process to removeinsoluble residues. Third, soymilk can also be reconstituted fromsoymilk powder by adding water. The soymilk may comprise from about 1%to about 50%, by weight (e.g., from about 5% to about 20%, by weight) ofsolids from the soybean.

The known active ingredients of soybeans include, but not limiting to,isoflavones, phytoestrogens, genistein, daidzein, glycitein, saponins,and phytosterols. The soybean extracts useful in this invention may beproduced from all soybean species, regardless of their geographicorigin, sun exposure, harvest time and the like. However, specificstrains, geographic origins or growth conditions might be preferred. Forexample, but not limiting to, soybean strains particularly rich in itsSoybean Trypsin Inhibitor (STI) content or in isoflavone content, orgrowth conditions that result in STI or isoflavone enrichment in thebean, might be preferred.

In one embodiment, the soybean extract is a non-denatured soybeanextract. “Denaturation” is defined in the Bantam Medical Dictionary(1990 edition) as “the change in the physical and the physiologicalproperties of a protein, that are brought about by heat, X-rays orchemicals. These changes include loss of activity (in the case ofenzymes) and loss (or alteration) of antigenicity (in the case ofantigens)”. What is meant by “non-denatured plant extract” is a productextracted or derived from a plant in which the processing for thederivation of such plant extract (e.g., the temperature, extractionmedia) did not eliminate its protease inhibitory activity. One suchprotease is trypsin. In one embodiment, the non-denatured state of thesoybean extract of this invention is measured by the presence of anintact soybean trypsin inhibitor (STI) protein, or by its trypsininhibitory activity.

It should be noted that the soybean extracts useful in the compositionsof this invention may have a distinctive odor. If necessary, the odor ofthe extracts may be reduced by using soybean products derived fromspecific strains of soybeans known to produce reduced-odor, including,but not limited to, lipoxygenase-2-deficient beans and those havingmodified sugar profile, and the like. A process to reduce oxygen levelsin the formulation may also reduce the odor. Various masking agents orfragrances may also be used to mask the odor. One way to make soymilk isto soak the soybeans in deionized or purified water for several hours,and grind them after they were fully hydrated, with the addition ofsmall quantities of water. The grinding process allows the soybean milkto be extracted. After collection, the soybean milk may be filtered toremove any residual parts of the bean husk.

The soymilk used in the formulations described below can be freshsoymilk as described above, or may be made from soybean powder andwater. The soybean powder is milled from soybeans and may also belyophilized, spray dried, or freeze-dried and the resulting soymilk mayor may not be filtered. Such prepared soymilk may have from about 1 toabout 90% by weight dry soybean powder. Another example is the use ofsoymilk powder, made from lyophilized, spray dried or freeze-driedsoymilk, with the addition of water and finished with or withoutfiltration or homogenization. Other methods of soybean extraction couldalso be used to create the active ingredients in the formulationsdescribed below. For example, the active ingredients could be extractedfrom ground soybeans using ethanol/water mixtures, followed by theremoval of the ethanol from the extract, in such ways that the serineprotease inhibitory activity of the soybean will be retained, andpreferably that the protein STI will remain intact.

In one embodiment, the soybean extracts utilized in the presentinvention have a microbial content of less than about 1,000 cfu per gram(such as less than about 100 cfu per gram) of the soybean extract.

The soybean extract may be exposed to gamma irradiation. The soybeanextract may be exposed to from about 2 to about 30 kGy of gammairradiation, such as from about 5 and about 10 kGy of gamma irradiation.Such treatment reduces the microbial content of the soybean extract,while maintaining its biological activity (e.g., serine proteaseinhibitory activity). The treatment of soybean extracts with gammairradiation maintains the cosmetic elegance of the composition, such asmaintained natural colors and does not induce significant malodors.

Other anti-microbial processes that also maintain the proteaseinhibitory activity of the soybean extract that can be practiced aloneor in combination with gamma irradiation, include, but are not limitedto, exposure to x-rays, high energy electron or proton beams,ultraviolet radiation, hydrostatic pressure, and addition of chemicalagents possessing antimicrobial activity, and combinations thereof.

Other Materials

Various other materials may also be present in the compositions usefulin the subject invention. These include humectants, proteins andpolypeptides, preservatives and an alkaline agent. Examples of suchagents are disclosed in the ICI Handbook, pp. 1650-1667. Thecompositions of the present invention may also contain chelating agents(e.g., EDTA) and preservatives (e.g., parabens). Examples of suitablepreservatives and chelating agents are listed in pp. 1626 and 1654-55 ofthe ICI Handbook. In addition, the compositions useful herein cancontain conventional cosmetic adjuvants, such as colorants such as dyesand pigments, opacifiers (e.g., titanium dioxide), and fragrances.

Mineral Water

The compositions of the present invention may be prepared using amineral water, for example mineral water that has been naturallymineralized such as Evian® Mineral Water (Evian, France). In oneembodiment, the mineral water has a mineralization of at least about 200mg/L (e.g., from about 300 mg/L to about 1000 mg/L). In one embodiment,the mineral water contains at least about 10 mg/L of calcium and/or atleast about 5 mg/L of magnesium.

Use

The composition according to the invention can be used to treat avariety of skin conditions, including but not, limited to acne. In oneembodiment, the composition is used to treat other sebum disorders suchas hyperlipidemia, hyperandrogenia, seborrhea, seborrheic dermatitis,seborrhea capitis, eczematoid seborrhea, seborrhea faciei, seborrheaoleosa, seborrhea sicca, seborrhea squamosa neonatorum, sebacioushyperplasia, Rosacea, follicular rash, demodex folliculorum, oily skin,Keratinous cyst, Pseudofolliculitis barbae and hypertrichosis.

The compositions of the present invention can also be used to reduce theappearance of pores and oil on the skin (e.g., the face, scalp, orhair).

The composition of the present invention can also be used to reduce acnelesions, comedones, or pimples, reduce the appearance of acne lesions,comedones, or pimples, reduces the appearance of acne breakouts andblemishes, prevent, control or regulate the appearance of acne breakoutsand blemishes, and reduce breakouts and blemishes.

The composition of the present invention can also be used to promote thereduction in the appearance of oil on the skin, such as reducing theappearance of sebum, preventing, controlling or regulating theproduction of sebum, reducing sebum, reducing the appearance ofoily/shiny skin, reducing the appearance of greasy skin, and reducingshine on the skin, hair, or scalp.

The composition and formulations containing such compositions of thepresent invention may be prepared using methodology that is well knownby an artisan of ordinary skill.

EXAMPLE 1 In Vitro Sebocyte Lipogenesis Assay

Samples of facial skin obtained from subjects undergoing faceliftsurgeries were used. Upon arrival, the top 0.4 mm skin section, obtainedby a dermatome was removed and the second 0.4 mm dermal section(previously shown to be rich in sebaceous glands) was used to isolatesebaceous cells. The tissue was digested with Dispase in Dulbecco'sModified Eagle Medium (DMEM) containing penicillin and streptomycin and10% calf serum for 20 min at 37° C., and then with 0.3% trypsin/0.1%ethylenediaminetetraacetic acid (EDTA) in phosphate buffered saline(PBS) for 10 min at 37° C. Single cell suspensions were obtained byscraping the tissue vigorously with a scalpel blade. The released cellswere seeded on a feeder layer of mitomycin C inactivated 3T3 fibroblastsand cultured in growth medium for 3 days at 37° C. The growth mediumcontained DMEM and F12 media (3:1), L-glutamine, sodium pyruvate,penicillin, streptomycin, 8% fetal bovine serum, 2% heat-inactivatedhuman serum, epidermal growth factor, insulin, hydrocortisone, andeither with or without cholera toxin (ChT). The cultures treated withChT were shifted to a low-serum medium for 3 days and followed by aserum-free medium for another 7 days for the induction of lipidformation and storage, while the cultures without ChT treatment weremaintained in growth medium (non-induced condition) for 10 days. Thelow-serum medium consisted of DMEM and F12 media (3:1) supplemented withL-glutamine, sodium pyruvate, penicillin, streptomycin, 2%heat-inactivated bovine serum and 2% heat-inactivated human serum, 1×insulin-transferrin-selenium, 1× trace elements. The serum-free mediumcontained DMEM and F12 media (3:1) supplemented with L-glutamine, sodiumpyruvate, penicillin, streptomycin, 1× insulin-transferrin-selenium, 1×trace elements, 3,3′,5-triiodo-L-thyronine sodium. For neutral lipidanalysis by Nile Red staining, cells were grown in 96-well plates andfor lipid analysis by thin layer chromatography, cells were grown in6-well plates and harvested at the end of the culturing by scraping.

Testing Stimulators or Inhibitors of Sebocyte Differentiation and LipidProduction

Hormones, mixture of hormones i.e. bovine pituitary extract or compoundsto be tested were added to the culture at the beginning of serum freemedia addition. Two criteria were used to evaluate the effect of thesematerials on sebaceous cultures: 1) visual observations and 2)evaluation of sebaceous lipid accumulation and synthesis. The evaluationof lipid accumulation completed using the Nile red method. This methodrelies on visualization of neutral lipids by Nile red and quantitationby reading of fluorescence at 535 nm excitation, 580 nm emission using aplate reader. The lipid synthesis was evaluated by radioactive labelingusing 14C acetate and quantified by Bio Rad Phosphoimager (MolecularImager, FX) using 4.1 Software.

Morphological evaluation of lipid accumulation was easily recognizedsince the cells enlarged displayed lipid granules that in bright fieldlight microscopy appeared as yellowish circles in the cells.Quantitation of accumulation/inhibition of neutral lipids in sebocyteswas accomplished by Nile red binding assay. Briefly, following exposureof sebocytes to test compounds, the cells were allowed to interact with1 μM Nile red in Hanks buffered saline solution containing DMSO andPluronic F127. After 4 hours of incubation, washing and incubationovernight, the fluorescence was read at 535 nm excitation and 580 nmemission using a fluorescence plate reader and compared to an inductionagent (i.e. cholera toxin). To determine whether the compounds had aninhibitory effect on cell growth, cell counts were performed.

Following the procedure described above, compounds of the presentinvention were tested for visual and Nile red evaluation of lipidaccumulation, the results of which are depicted in Table 1.

TABLE 1 % Reduction % Reduction in Lipid in Lipid Synthesis in Synthesisin Sebocytes Sebocytes Structure [3 uM] Structure [3 uM]

12.4

Not Active

12.8

Not Active

20.5

Not Active

25.6

Not Active

26.9

Not Active

28.4

Not Active

28.7

Not Active

47.3

Not Active

Not Active

Not Active

Not Active

Not Active

Not Active

Not Active

Not Active

Not Active

Not Active

Not Active

Not Active

Not Active

Not Active

Not Active

In the same assay, synergism between the chalcones of the presentinvention and Green Tea extract was also found (See Table 2).

TABLE 2 2,2′-dihydroxy- Green Tea Extract chalcone % Cholera ToxinConcentration Concentration Reduction 0.0 μg/mL 3.0 μM 50.8 0.0 μg/mL1.0 μM 38.2 0.0 μg/mL 0.3 μM 14.3 1.25 μg/mL    0 μM 13.3 2.5 μg/mL   0μM 24.2 1.25 μg/mL  3.0 μM 71.1 2.5 μg/mL 3.0 μM 84.1 1.25 μg/mL  1.0 μM63.3 2.5 μg/mL 1.0 μM 77.1 1.25 μg/mL  0.3 μM 46.5 2.5 μg/mL 0.3 μM 65.9

1. A method of treating acne or reducing the appearance of oil or poreson the skin, said method comprising administering to skin in need ofsuch treatment a composition comprising a chalcone of Formula I

wherein, R is hydrogen, C₁-C₆ alkyl, C₂-C₁₀ alkenyl, acyl or glycosyl,and m is 0 to 5; and n is 0 to 5; or a cosmetically-acceptable saltthereof; provided that the sum of m and n is greater than or equal to 4.2. A method of treating acne or reducing the appearance of oil or poreson the skin, said method comprising administering to skin in need ofsuch treatment a composition comprising (a) a chalcones of Formula I

wherein, R is hydrogen, C₁-C₆ alkyl, C₂-C₁₀ alkenyl, acyl or glycosyl,and m is 0 to 5; n is 0 to 5; or a cosmetically-acceptable salt thereof;and (b) a catechin.
 3. A method of claim 2, wherein said catechin isselected from the group consisting of catechin, catechin gallate,epicatechin, gallocatechin, gallocatechin gallate, epigallocatechin,epicatechin gallate, and epigallocatechin gallate.
 4. A method of claim1, wherein said chalcone is 2′-hydroxy-2,3,5′-trimethoxychalcone, anenantiomer thereof, or a diastereoisomer thereof, or a cosmeticallyacceptable salt thereof.
 5. A method of claim 2, wherein said chalconeis selected from the group consisting of 2,2′-dihydroxychalcone and2′-hydroxy-2,3,5′-trimethoxychalcone, an enantiomer thereof, or adiastereoisomer thereof, or a cosmetically acceptable salt thereof
 6. Amethod of claim 3, wherein said chalcone is selected from the groupconsisting of 2,2′-dihydroxychalcone and2′-hydroxy-2,3,5′-trimethoxychalcone, an enantiomer thereof, or adiastereoisomer thereof, or a cosmetically acceptable salt thereof.
 7. Amethod of claim 1, wherein said method comprises treating acne.
 8. Amethod of claim 2, wherein said method comprises treating acne.
 9. Amethod of claim 1, wherein said method comprises reducing the appearanceof oil or pores on the skin in skin in not in need for treatment foracne.
 10. A method of claim 2, wherein said method comprises reducingthe appearance of oil or pores on the skin in skin in not in need fortreatment for acne.
 11. A method of claim 1, wherein said compositionfurther comprises salicylic acid or benzoyl peroxide.
 12. A method ofclaim 2, wherein said composition further comprises salicylic acid orbenzoyl peroxide.
 13. A method of claim 3, wherein said compositionfurther comprises salicylic acid or benzoyl peroxide.
 15. A method ofclaim 5, wherein said composition further comprises salicylic acid orbenzoyl peroxide.
 16. A method of claim 6, wherein said compositionfurther comprises salicylic acid or benzoyl peroxide.
 17. A productcomprising: (a) a composition comprising a chalcone of Formula I

wherein, R is hydrogen, C₁-C₆ alkyl, C₂-C₁₀ alkenyl, acyl or glycosyl,and m is 0 to 5; and n is 0 to 5; or a cosmetically-acceptable saltthereof; provided that the sum of m and n is greater than or equal to 4;and (b) instructions directing the user to administer said compositionto skin in order to treat acne or reduce the appearance of oil or poreson the skin.
 18. A product of claim 17, wherein said instructions directthe user to administer said composition to treat acne.
 19. A product ofclaim 17, wherein said composition further comprises salicylic acid orbenzoyl peroxide.
 20. A product of claim 18, wherein said compositionfurther comprises salicylic acid or benzoyl peroxide.